Efficacy of Xeljanz, Biologics, & DMARDs in Rheumatoid Disease

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Why should I feel like I failed? I’m not alone

ACR20 responses shown as pie chartWe probably agree it’s unfair to say, “patients fail treatments” instead of the reverse, but there is still disappointment. I was optimistic that my Rheumatoid disease would respond to Xeljanz, the new oral DMARD (disease modifying anti-rheumatic drug) from Pfizer. Unfortunately, my joint stiffness and inflammation, hoarseness, and fevers continued. However, the vascular rash on my leg (diagnosed as livedo reticularis) improved while taking Xeljanz, and it worsened after I stopped taking it.

Should any of this help you decide whether to try Xeljanz? Probably not. The data shows:

  • a difference exists between placebo and tofacitinib (Xeljanz);
  • a wide variety of response exists between patients; and
  • a small minority respond really well.

Tofacitinib efficacy Table1

A minority has an excellent response to Xeljanz and Biologics

The efficacy data with Xeljanz differ among their various trials, but they are similar. And response levels are comparable to those of Biologics, using ACR20, ACR50, and ACR70. Three years ago on RAW, we discussed some comparisons of efficacy of Biologics, according to a Cochrane review of 31 studies of ACR50 and Danish study of ACR70. Looking at trial data and comparison studies, on average, about 34% are non-responders, which means they do not meet the primary endpoint of ACR20 (an assessment of 20% improvement according to specific measures of disease activity). The remaining 66%, considered responders, are divided between ACR20, ACR50, and ACR70. On average, 20% or fewer people experience 70 percent improvement, and about 29% reach ACR20 only. The remainder are ACR50 only.

Non-overlapping ACR 20 comparisonRemember, the ACR response levels are usually reported with all higher responses included, so the traditional ACR20 number includes all responders (including ACR50 and ACR70). It may be easier to understand showing all groups separated in a traditional pie chart (see images to right and at top). That method is discussed here on RAW: New Way to Report Response in RA Clinical Trials?

Are Biologics and Xeljanz more effective than traditional DMARDs like methotrexate?

Sometimes people assume that shots are stronger than pills, and IV infusions are stronger than shots. But that’s not accurate; the medications work by different mechanisms, so they are effective on different patients with different disease mechanisms and progression of disease. It’s true that Biologics and Xeljanz are considered more effective than other DMARDs, but that could be misleading in some ways: To people who respond well to methotrexate alone, or even Plaquenil, DMARDs are sufficiently effective.

The complexity of Rheumatoid disease, its heterogeneity, and tendency to change in the same patient over time all complicate measurement of efficacy, as well as development of new treatments.

That said, traditional DMARDs are considered less effective, and this has been shown in head to head studies. As a matter of fact, one thing companies do during trials is attempt to show their new product is more effective than methotrexate. As RAW reported last year, Xeljanz was found superior to methotrexate. A couple of years ago, RAW reported on testing of a new possible methotrexate alternative and a British Medical Journal review of methotrexate studies showing 46% reached ACR20 and only 23% reached ACR50 (by the inclusive method).

Screenshot of methotrexate response rate Blackwell Publishing

Some trials have also compared combinations of DMARDs together (triple therapy) or combinations of a DMARD and a Biologic. So far, it has often been concluded that methotrexate with a Biologic is best at preventing radiologic damage (joint damage as studied on x-ray).

Bottom line for Rheumatoid patients choosing therapies

The bottom line is that some respond very well to currently available therapies, but the range of responses is wide, and there is no way to predict yet which treatment or combination will work best. As we discussed recently on RAW, people often weigh risks and benefits for choices, including medications. It has been my own personal choice to try every opportunity available to increase function and get relief from pain, and I’ve made that choice with no regrets.

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Kelly Young. All rights reserved.

This entry was posted on Monday, May 13th, 2013 at 10:00 am and is filed under RA Education, Reality Check. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

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